Several arene oxides and epoxides are known to react covalently with macromolecules, including nucleic acids, and to transform cells in vitro, suggesting their role as ultimate carcinogens, mutagens, and cytotoxins. We are studying the further metabolism of arene oxides and epoxides by soluble fraction glutathione S-transferases and microsomal epoxide hydrase in liver, lung, kidney, testis, and intestinal mucosa of adult and immature rats, rabbits, and guinea pigs. The relative importance of the two pathways for selected epoxides and arene oxides is being assessed in isolated perfused liver and lung, preparations which have intact cellular structures.